Follistatin / FS344

ID: follistatin_fs344

Aliases: Follistatin-344, FST-344, FS344, AAV1-FS344, rAAV1.CMV.huFollistatin344, follistatin gene therapy

Type: compound_family

Route/form: intramuscular AAV1-FS344 gene transfer in published clinical studies; gray-market peptide/injection route is not clinically established

Status: investigational_or_research

Evidence level: early human

Best data tier: early human

Support scope: human, non-human/mechanistic, review/regulatory

Source types: early_human, evidence_report, human_trial, preclinical, review

Linked sources: 7

Broad outcomes: Fat loss / metabolic health, Muscle growth / performance / recovery, PEDs / AAS / thermogenics, Safety / regulatory

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• myostatin binding/inhibition
• activin binding/inhibition
• TGF-beta family ligand sequestration
• muscle hypertrophy and satellite-cell signaling

Optimization domains

• myostatin
• activin signaling
• muscle
• muscle hypertrophy
• muscle wasting
• Becker muscular dystrophy
• inclusion body myositis
• gene therapy
• body composition
• doping

Research basis

• AAV1-FS344 has early human disease-context evidence in Becker muscular dystrophy and sporadic inclusion body myositis, plus non-human-primate data showing local muscle size and strength increases after gene delivery.
• Mechanistically, follistatin is broader than a pure myostatin antibody: it can bind myostatin and activins, which fits the larger myostatin/activin pathway cluster that includes ACE-031, bimagrumab, trevogrumab, garetosmab, and apitegromab.
• The preclinical muscle literature supports a plausible hypertrophy mechanism involving both ligand inhibition and satellite-cell/protein-synthesis biology.

Limits, risks, and missing evidence

• The strongest direct data are intramuscular AAV gene-therapy studies in muscle disease, not injectable research peptide use, bodybuilding use, obesity add-on use, or healthy-user performance optimization.
• The IBM efficacy claim has a published critique about trial design, comparator choice, post hoc outcomes, and safety interpretation; this should be read as early signal, not settled efficacy.
• Follistatin is not myostatin-only. Activin/pituitary-gonadal/reproductive-axis biology, off-target tissue effects, immune responses to AAV/vector/transgene, durability, reversibility, and long-term safety remain major unknowns.

Risk flags

• gene therapy context
• myostatin activin axis
• off target axis risk
• immune vector risk
• not gray market peptide evidence

Linked papers, labels, and reviews

1. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy
   early_human / pubmed_follistatin_bmd_phase12a_2015
   Open-label AAV1-FS344 intramuscular gene-transfer study in Becker muscular dystrophy; useful human disease-context anchor for follistatin gene therapy, not healthy-user hypertrophy evidence.
2. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy
   early_human / pubmed_follistatin_bmd_ambulation_2015
   Becker muscular dystrophy follistatin gene-therapy follow-up/clinical interpretation paper; relevant to ambulation and FS344 rationale.
3. Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes
   human_trial / pubmed_follistatin_sibm_trial_2017
   Open-label sIBM AAV-FS344 gene-therapy report; relevant early human signal, but trial design and efficacy claims need the critique source alongside it.
4. Unfounded Claims of Improved Functional Outcomes Attributed to Follistatin Gene Therapy in Inclusion Body Myositis
   evidence_report / pmc_follistatin_sibm_critique_2017
   Published critique arguing the IBM trial design and outcome handling do not support strong efficacy conclusions; important skepticism source for this entry.
5. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates
   preclinical / pubmed_follistatin_nhp_gene_delivery_2009
   AAV1-FS344 non-human-primate study reporting local muscle size and strength effects after intramuscular gene delivery; key translational mechanism source.
6. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease
   review / pubmed_follistatin_myostatin_therapy_review_2009
   Review focused on follistatin/myostatin inhibition as muscle-disease therapy; useful for broad mechanism and development context.
7. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin
   preclinical / pubmed_follistatin_activin_myostatin_muscle_2009
   Mouse/mechanistic study showing follistatin muscle effects involve both myostatin and activin inhibition plus satellite-cell proliferation, not a clean myostatin-only switch.